Pain clinic surveys indicate that 20-25% of chronic pain complaints invovle the orofacial region (NIDR, 1985). Of these cases approximately 75% are diagnosed as musculoskeletal pain. In view of the significant incidence of TMJ-related pain reports and their relation to muscular pain, we have chosen in the Research Experience portion of the proposed study to investigate the transmission and modulation of nociceptive information by primary afferents located in the TMJ capsule. First, anatomical studies tracing the afferent innervation form the TMJ capsule to the brain stem and the first and second segments of the cervical spinal cord in the rat will be performed using horseradish peroxidase labeling. Next, characterization of the response properties of secondary neurons involved in nociceptive transmission from the TMJ to the thalamus will be performed using electrophysiology. Cells will be characterized as low threshold (LT), wide-dynamic range (WDR) or high threshold (HT) neurons by studying their response to different stimulus modalities (i.e. mechanical, thermal, electrical, chemical). Next, microiontophoresis will be used to study the response of cells, responsive to noxious stimuli (WDR and HT), to analgesic drugs and neurotransmitters (opioid peptides, neurokinins and excitatory amino acid (EAA, e.g. glutamate) agonists and antagonists). The neuroanatomical, neuropharmacological and neurophysiological studies of the trigeminal sensory nuclear complex proposed here should serve to shed some light on the mechanisms of nociception involved in TMJ-related pain. The proposed studies might also provide some insight into potentially useful treatments for the clinical setting.